Risperidone (depot) for schizophrenia.

A variety of alpha-blockers are used for treating lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Silodosin is a novel, more selective alpha-blocker, which is specific to the lower urinary tract and may have fewer side effects than other alpha-blockers. To assess the effects of silodosin for the treatment of LUTS in men with BPH. We performed a comprehensive search using multiple databases (Cochrane Library, MEDLINE, EMBASE, Scopus, Google Scholar, and Web of Science), trials registries, other sources of grey literature, and conference proceedings with no restrictions on the language of publication or publication status up until 13 June 2017. We included all parallel, randomized controlled trials. We also included cross-over designs. Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of evidence according to the GRADE approach. We included 19 unique studies with 4295 randomized participants across four comparisons for short-term follow-up. The mean age, prostate volume, and International Prostate Symptom Score were 66.5 years, 38.2 mL, and 19.1, respectively. Silodosin versus placeboBased on four studies with a total of 1968 randomized participants, silodosin may reduce urologic symptom scores in an appreciable number of men (mean difference (MD) -2.65, 95% confidence interval (CI) -3.23 to -2.08; low-quality evidence). Silodosin likely does not result in a clinically important reduction in quality of life (MD -0.42, 95% CI -0.71 to -0.13; moderate-quality evidence). It may not increase rates of treatment withdrawal for any reason (relative risk (RR) 1.08, 95% CI 0.70 to 1.66; low-quality evidence). We are uncertain about the effect of silodosin on cardiovascular adverse events (RR 1.28, 95% CI 0.67 to 2.45; very low-quality evidence). Silodosin likely increases sexual adverse events (RR 26.07, 95% CI 12.36 to 54.97; moderate-quality evidence); this would result in 180 more sexual adverse events per 1000 men (95% CI 82 more to 388 more). Silodosin versus tamsulosinBased on 13 studies with a total of 2129 randomized participants, silodosin may result in little to no difference in urologic symptom scores (MD -0.04, 95% CI -1.31 to 1.24; low-quality evidence) and quality of life (MD -0.15, 95% CI -0.53 to 0.22; low-quality evidence). We are uncertain about treatment withdrawals for any reason (RR 1.02, 95% CI 0.62 to 1.69; very low-quality evidence). Silodosin may result in little to no difference in cardiovascular adverse events (RR 0.77, 95% CI 0.53 to 1.12; low-quality evidence). Silodosin likely increases sexual adverse events (RR 6.05, 95% CI 3.55 to 10.31; moderate-quality evidence); this would result in 141 more sexual adverse events per 1000 men (95% CI 71 more to 261 more). Silodosin versus naftopidilBased on five studies with a total of 763 randomized participants, silodosin may result in little to no differences in urologic symptom scores (MD -0.85, 95% CI -2.57 to 0.87; low-quality evidence), quality of life (MD -0.17, 95% CI -0.60 to 0.27; low-quality evidence), treatment withdrawal for any reason (RR 1.25, 95% CI 0.81 to 1.93; low-quality evidence), and cardiovascular adverse events (RR 1.02, 95% CI 0.41 to 2.56; low-quality evidence). Silodosin likely increases sexual adverse events (RR 5.93, 95% CI 2.16 to 16.29; moderate-quality evidence); this would result in 74 more sexual adverse events per 1000 men (95% CI 17 more to 231 more). Silodosin versus alfuzosinBased on two studies with a total of 155 randomized participants, silodosin may or may not result in a clinically important increase in urologic symptom scores (MD 3.83, 95% CI 0.12 to 7.54; low-quality evidence). Silodosin likely results in little to no difference in quality of life (MD 0.14, 95% CI -0.46 to 0.74; moderate-quality evidence). We found no event of treatment withdrawal for any reason. Silodosin may not reduce cardiovascular adverse events (RR 0.67, 95% CI 0.36 to 1.24; low-quality evidence) but likely increases sexual adverse events (RR 37.21, 95% CI 5.32 to 260.07; moderate-quality evidence); this would result in 217 more sexual adverse events per 1000 men (95% CI 26 more to 1000 more). Silodosin may reduce urologic symptom scores in an appreciable number of men compared to placebo. Quality of life and treatment withdrawals for any reason appears similar. Its efficacy appears similar to that of other alpha blockers (tamsulosin, naftopidil and alfuzosin) but the rate of sexual side effects is likely higher. Our certainty in the estimates of effect was lowered due to study limitations, inconsistency and imprecision.

Cognitive behavioural therapy (CBT) is a psychosocial treatment that aims to re-mediate distressing emotional experiences or dysfunctional behaviour by changing the way in which a person interprets and evaluates the experience or cognates on its consequence and meaning. This approach helps to link the person's feelings and patterns of thinking which underpin distress. CBT is now recommended by the National Institute for Health and Care Excellence (NICE) as an add-on treatment for people with a diagnosis of schizophrenia. This review is also part of a family of Cochrane CBT reviews for people with schizophrenia. To assess the effects of cognitive behavioural therapy added to standard care compared with standard care alone for people with schizophrenia. We searched the Cochrane Schizophrenia Group's Trials Register (up to March 6, 2017). This register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. We selected all randomised controlled clinical trials (RCTs) involving people diagnosed with schizophrenia or related disorders, which compared adding CBT to standard care with standard care given alone. Outcomes of interest included relapse, rehospitalisation, mental state, adverse events, social functioning, quality of life, and satisfaction with treatment.We included studies fulfilling the predefined inclusion criteria and reporting useable data. We complied with the Cochrane recommended standard of conduct for data screening and collection. Where possible, we calculated relative risk (RR) and its 95% confidence interval (CI) for binary data and mean difference (MD) and its 95% confidence interval for continuous data. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. This review now includes 60 trials with 5,992 participants, all comparing CBT added to standard care with standard care alone. Results for the main outcomes of interest (all long term) showed no clear difference between CBT and standard care for relapse (RR 0.78, 95% CI 0.61 to 1.00; participants = 1538; studies = 13, low-quality evidence). Two trials reported global state improvement. More participants in the CBT groups showed clinically important improvement in global state (RR 0.57, 95% CI 0.39 to 0.84; participants = 82; studies = 2 , very low-quality evidence). Five trials reported mental state improvement. No differences in mental state improvement were observed (RR 0.81, 95% CI 0.65 to 1.02; participants = 501; studies = 5, very low-quality evidence). In terms of safety, adding CBT to standard care may reduce the risk of having an adverse event (RR 0.44, 95% CI 0.27 to 0.72; participants = 146; studies = 2, very low-quality evidence) but appears to have no effect on long-term social functioning (MD 0.56, 95% CI -2.64 to 3.76; participants = 295; studies = 2, very low-quality evidence, nor on long-term quality of life (MD -3.60, 95% CI -11.32 to 4.12; participants = 71; study = 1, very low-quality evidence). It also has no effect on long-term satisfaction with treatment (measured as 'leaving the study early') (RR 0.93, 95% CI 0.77 to 1.12; participants = 1945; studies = 19, moderate-quality evidence). Relative to standard care alone, adding CBT to standard care appears to have no effect on long-term risk of relapse. A very small proportion of the available evidence indicated CBT plus standard care may improve long term global state and may reduce the risk of adverse events. Whether adding CBT to standard care leads to clinically important improvement in patients' long-term mental state, quality of life, and social function remains unclear. Satisfaction with care (measured as number of people leaving the study early) was no higher for participants receiving CBT compared to participants receiving standard care. It should be noted that although much research has been carried out in this area, the quality of evidence available is poor - mostly low or very low quality and we still cannot make firm conclusions until more high quality data are available.

Stable angina pectoris is a chronic medical condition with significant impact on mortality and quality of life; it can be macrovascular or microvascular in origin. Ranolazine is a second-line anti-anginal drug approved for use in people with stable angina. However, the effects of ranolazine for people with angina are considered to be modest, with uncertain clinical relevance. To assess the effects of ranolazine on cardiovascular and non-cardiovascular mortality, all-cause mortality, quality of life, acute myocardial infarction incidence, angina episodes frequency and adverse events incidence in stable angina patients, used either as monotherapy or as add-on therapy, and compared to placebo or any other anti-anginal agent. We searched CENTRAL, MEDLINE, Embase and the Conference Proceedings Citation Index - Science in February 2016, as well as regional databases and trials registers. We also screened reference lists. Randomised controlled trials (RCTs) which directly compared the effects of ranolazine versus placebo or other anti-anginals in people with stable angina pectoris were eligible for inclusion. Two authors independently selected studies, extracted data and assessed risk of bias. Estimates of treatment effects were calculated using risk ratios (RR), mean differences (MD) and standardised mean differences (SMD) with 95% confidence intervals (CI) using a fixed-effect model. Where we found statistically significant heterogeneity (Chi² P < 0.10), we used a random-effects model for pooling estimates. Meta-analysis was not performed where we found considerable heterogeneity (I² ≥ 75%). We used GRADE criteria to assess evidence quality and the GRADE profiler (GRADEpro GDT) to import data from Review Manager 5.3 to create 'Summary of findings' tables. We included 17 RCTs (9975 participants, mean age 63.3 years). We found very limited (or no) data to inform most planned comparisons. Summary data were used to inform comparison of ranolazine versus placebo. Overall, risk of bias was assessed as unclear.For add-on ranolazine compared to placebo, no data were available to estimate cardiovascular and non-cardiovascular mortality. We found uncertainty about the effect of ranolazine on: all-cause mortality (1000 mg twice daily, RR 0.83, 95% CI 0.26 to 2.71; 3 studies, 2053 participants; low quality evidence); quality of life (any dose, SMD 0.25, 95% CI -0.01 to 0.52; 4 studies, 1563 participants; I² = 73%; moderate quality evidence); and incidence of non-fatal acute myocardial infarction (AMI) (1000mg twice daily, RR 0.40, 95% CI 0.08 to 2.07; 2 studies, 1509 participants; low quality evidence). Add-on ranolazine 1000 mg twice daily reduced the fervour of angina episodes (MD -0.66, 95% CI -0.97 to -0.35; 3 studies, 2004 participants; I² = 39%; moderate quality evidence) but increased the risk of non-serious adverse events (RR 1.22, 95% CI 1.06 to 1.40; 3 studies, 2053 participants; moderate quality evidence).For ranolazine as monotherapy compared to placebo, we found uncertain effect on cardiovascular mortality (1000 mg twice daily, RR 1.03, 95% CI 0.56 to 1.88; 1 study, 2604 participants; low quality evidence). No data were available to estimate non-cardiovascular mortality. We also found an uncertain effect on all-cause mortality for ranolazine (1000 mg twice daily, RR 1.00, 95% CI 0.81 to 1.25; 3 studies, 6249 participants; low quality evidence), quality of life (1000 mg twice daily, MD 0.28, 95% CI -1.57 to 2.13; 3 studies, 2254 participants; moderate quality evidence), non-fatal AMI incidence (any dose, RR 0.88, 95% CI 0.69 to 1.12; 3 studies, 2983 participants; I² = 50%; low quality evidence), and frequency of angina episodes (any dose, MD 0.08, 95% CI -0.85 to 1.01; 2 studies, 402 participants; low quality evidence). We found an increased risk for non-serious adverse events associated with ranolazine (any dose, RR 1.50, 95% CI 1.12 to 2.00; 3 studies, 947 participants; very low quality evidence). We found very low quality evidence showing that people with stable angina who received ranolazine as monotherapy had increased risk of presenting non-serious adverse events compared to those given placebo. We found low quality evidence indicating that people with stable angina who received ranolazine showed uncertain effect on the risk of cardiovascular death (for ranolazine given as monotherapy), all-cause death and non-fatal AMI, and the frequency of angina episodes (for ranolazine given as monotherapy) compared to those given placebo. Moderate quality evidence indicated that people with stable angina who received ranolazine showed uncertain effect on quality of life compared with people who received placebo. Moderate quality evidence also indicated that people with stable angina who received ranolazine as add-on therapy had fewer angina episodes but increased risk of presenting non-serious adverse events compared to those given placebo.

How effective are interventions to reduce Staphylococcus aureus in eczema?

Interventions to reduce Staphylococcus aureus in the management of eczema.

Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain. To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any other pharmacological agent in patients with Buerger's disease. The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature; screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies. Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease. Two review authors, independently assessed the studies, extracted data and performed data analysis. Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid.Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; one study; moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; one study; moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; one study; moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; two studies; I² = 0%; very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; one study; low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; one study; moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; one study; moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; one study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence).Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study.Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure. Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.

RV1 and RV5 prevent episodes of rotavirus diarrhoea. The vaccine efficacy is lower in high-mortality countries; however, due to the higher burden of disease, the absolute benefit is higher in these settings. No increased risk of serious adverse events including intussusception was detected, but post-introduction surveillance studies are required to detect rare events associated with vaccination.

Background Pityriasis rosea is a scaly, itchy rash that mainly affects young adults and lasts for 2 to 12 weeks. The effects of many available treatments are uncertain. This is an update of a Cochrane Review first published in 2007. Objectives To assess the effects of interventions for the management of pityriasis rosea in any individual diagnosed by a medical practitioner. Search methods We updated our searches of the following databases to October 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched five trials registers. We also checked the reference lists of included and excluded studies, contacted trial authors, scanned the abstracts from major dermatology conference proceedings, and searched the CAB Abstracts database. We searched PubMed for adverse effects to November 2018. Selection criteria Randomised controlled trials of interventions in pityriasis rosea. Treatment could be given in a single therapy or in combination. Eligible comparators were no treatment, placebo, vehicle only, another active compound, or placebo radiation treatment. Data collection and analysis We used standard methodological procedures expected by the Cochrane. Our key outcomes were good or excellent rash improvement within two weeks, rated separately by the participant and medical practitioner; serious adverse events; resolution of itch within two weeks (participant‐rated); reduction in itch score within two weeks (participant‐rated); and minor participant‐reported adverse events not requiring withdrawal of the treatment. Main results We included 14 trials (761 participants). In general, risk of selection bias was unclear or low, but risk of performance bias and reporting bias was high for 21% of the studies. Participant age ranged from 2 to 60 years, and sex ratio was similar. Disease severity was measured by various severity indices, which the included studies did not categorise. Six studies were conducted in India, three in Iran, two in the Philippines, and one each in Pakistan, the USA, and China. The included studies were conducted in dermatology departments and a paediatric clinic. Study duration ranged from 5 to 26 months. Three studies were funded by drug manufacturers; most studies did not report their funding source. The included studies assessed macrolide antibiotics, an antiviral agent, phototherapy, steroids and antihistamine, and Chinese medicine. None of the studies measured participant‐rated good or excellent rash improvement. All reported outcomes were assessed within two weeks of treatment, except for adverse effects, which were measured throughout treatment. There is probably no difference between oral clarithromycin and placebo in itch resolution (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.47 to 1.52; 1 study, 28 participants) or rash improvement (medical practitioner‐rated) (RR 1.13, 95% CI 0.89 to 1.44; 1 study, 60 participants). For this comparison, there were no serious adverse events (1 study, 60 participants); minor adverse events and reduction in itch score were not measured; and all evidence was of moderate quality. When compared with placebo, erythromycin may lead to increased rash improvement (medical practitioner‐rated) (RR 4.02, 95% CI 0.28 to 56.61; 2 studies, 86 participants, low‐quality evidence); however, the 95% CI indicates that the result may also be compatible with a benefit of placebo, and there may be little or no difference between treatments. Itch resolution was not measured, but one study measured reduction in itch score, which is probably larger with erythromycin (MD 3.95, 95% CI 3.37 to 4.53; 34 participants, moderate‐quality evidence). In the same single, small trial, none of the participants had a serious adverse event, and there was no clear difference between groups in minor adverse events, which included gastrointestinal upset (RR 2.00, CI 0.20 to 20.04; moderate‐quality evidence). Two trials compared oral azithromycin to placebo or vitamins. There is probably no difference between groups in itch resolution (RR 0.83, 95% CI 0.28 to 2.48) or reduction in itch score (MD 0.04, 95% CI −0.35 to 0.43) (both outcomes based on one study; 70 participants, moderate‐quality evidence). Low‐quality evidence from two studies indicates there may be no difference between groups in rash improvement (medical practitioner‐rated) (RR 1.02, 95% CI 0.52 to 2.00; 119 participants). In these same two studies, no serious adverse events were reported, and there was no clear difference between groups in minor adverse events, specifically mild abdominal pain (RR 5.82, 95% CI 0.72 to 47.10; moderate‐quality evidence). Acyclovir was compared to placebo, vitamins, or no treatment in three trials (all moderate‐quality evidence). Based on one trial (21 participants), itch resolution is probably higher with placebo than with acyclovir (RR 0.34, 95% CI 0.12 to 0.94); reduction in itch score was not measured. However, there is probably a significant difference between groups in rash improvement (medical practitioner‐rated) in favour of acyclovir versus all comparators (RR 2.45, 95% CI 1.33 to 4.53; 3 studies, 141 participants). Based on the same three studies, there were no serious adverse events in either group, and there was probably no difference between groups in minor adverse events (only one participant in the placebo group experienced abdominal pain and diarrhoea). One trial compared acyclovir added to standard care (calamine lotion and oral cetirizine) versus standard care alone (24 participants). The addition of acyclovir may lead to increased itch resolution (RR 4.50, 95% CI 1.22 to 16.62) and reduction in itch score (MD 1.26, 95% CI 0.74 to 1.78) compared to standard care alone. Rash improvement (medical practitioner‐rated) was not measured. The trial reported no serious adverse events in either group, and there may be no difference between groups in minor adverse events, such as headache (RR 7.00, 95% CI 0.40 to 122.44) (all results based on low‐quality evidence). Authors' conclusions When compared with placebo or no treatment, oral acyclovir probably leads to increased good or excellent, medical practitioner‐rated rash improvement. However, evidence for the effect of acyclovir on itch was inconclusive. We found low‐ to moderate‐quality evidence that erythromycin probably reduces itch more than placebo. Small study sizes, heterogeneity, and bias in blinding and selective reporting limited our conclusions. Further research is needed to investigate different dose regimens of acyclovir and the effect of antivirals on pityriasis rosea.

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been implicated in the development and relapse of psychotic disorders. Elevated cortisol secretion has been positively linked with symptom severity in people with psychosis. Antiglucocorticoid and related drugs that target the HPA axis may be useful for the treatment of individuals with psychosis. 1. To determine the effects of antiglucocorticoid and related drugs for the treatment of psychosis, when used alone or in combination with antipsychotic medication.2. To determine whether the effects of these medications differs between those in a prodromal phase or first episode of psychosis, and those with more established illness. We searched the Cochrane Schizophrenia Group's Trials Register (August 2009 and April 2014). Randomised controlled trials (RCTs) comparing antiglucocorticoid and related drugs compared to placebo (either as a sole treatment or as an adjunct to atypical antipsychotics, typical antipsychotics, antidepressants or other combination treatment) for people with a primary diagnosis of a psychotic disorder, or for individuals at high risk of developing a psychotic disorder. Review authors independently selected trials, assessed methodological quality and extracted data. We used a fixed-effect meta-analysis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MDs) and standardised mean differences (SMDs) with 95% CIs for continuous measures. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table. We included 11 studies that randomly assigned 509 people with schizophrenia, schizoaffective disorder or psychotic depression. No trials were conducted in patients at their first episode of psychotic illness and none included populations at high risk for developing psychosis. Our pre-stated outcomes of interest were mental state, global state, general functioning, adverse effects and quality of life.Two trials compared antiglucocorticoid drugs (mifepristone) versus placebo as sole treatment. Limited data from one trial showed no difference in the proportion responding to mifepristone when mental state was assessed immediately post intervention using the Brief Psychiatric Rating Scale (BPRS) (n = 5, 1 RCT, MD -5.20, 95% CI -17.91 to 7.51; very low-quality evidence); depressive symptoms (Hamilton Rating Scale for Depression (HAMD) total) were also similar between groups (n = 5, 1 RCT, MD 1.67, 95% CI -16.44 to 19.78; very low-quality evidence). However, a significant difference favoured treatment at short-term follow-up for global state (30% reduction in total BPRS, n = 221, 1 RCT, RR 0.58, 95% CI 0.38 to 0.89; low-grade quality evidence). This effect was also seen for short-term positive psychotic symptoms (50% reduction in BPRS positive symptom subscale, n = 221, 1 RCT, RR 0.60, 95% CI 0.43 to 0.84; low-grade quality evidence). Participants receiving mifepristone experienced a similar overall number of adverse effects as those receiving placebo (n = 226, 2 RCTs, RR 0.92, 95% CI 0.77 to 1.09; moderate-quality evidence). No data on general functioning or quality of life were available.One trial compared an antiglucocorticoid, dehydroepiandrosterone (DHEA), as an adjunct to atypical antipsychotic treatment to adjunctive placebo. Data for main outcomes of interest were of low quality, and analysis of useable data showed no significant effects of treatment on mental state or adverse effects. Data on global state, general functioning and quality of life were not available.Data from six trials comparing antiglucocorticoid drugs as an adjunct to combination treatment versus adjunctive placebo showed no significant differences between groups in mean endpoint scores for overall psychotic symptoms (n = 171, 6 RCTs, SMD 0.01, 95% CI - 0.29 to 0.32) or positive psychotic symptoms (n = 151, 5 RCTs, SMD -0.07, 95% CI - 0.40 to 0.25). Data from three trials showed no differences between groups in mean endpoint scores for negative symptoms (n = 94, 3 RCTs, MD 2.21, 95% CI -0.14 to 4.55). One study found improvements in global state that were similar between groups (n = 30, 1 RCT, RR 0.58, 95% CI 0.32 to 1.06; very low-quality evidence). In this comparison, pooled results showed that antiglucorticoids caused a greater overall number of adverse events (n = 199, 7 RCTs, RR 2.66, 95% CI 1.33 to 5.32; moderate quality evidence), but no quality of life data were available. Good evidence is insufficient to conclude whether antiglucocorticoid drugs provide effective treatment for psychosis. Some global state findings suggest a favourable effect for mifepristone, and a few overall adverse effect findings favour placebo. Additional large randomised controlled trials are needed to justify findings.

Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European countries and Japan. To examine the clinical effects and safety of perphenazine for those with schizophrenia and schizophrenia-like psychoses. We updated our original search using the Cochrane Schizophrenia Group's register (September 2013), references of all included studies and contacted pharmaceutical companies and authors of included studies in order to identify further trials. We included all randomised controlled trials that compared perphenazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. We excluded trials of depot formulations of perphenazine. Two review authors independently inspected citations and, where possible, abstracts. We ordered papers, inspected and quality assessed them. We extracted data, again working independently. If loss to follow-up was greater than 50% we considered results as 'prone to bias'. For dichotomous data, we calculated risk ratios (RR) and for continuous data we calculated mean differences (MD), both with the 95% confidence intervals (CI). We assessed quality of data using the GRADE (Grading of Recommendations Assessment, Development and Evaluationtool) and assessed risk of bias for included studies. Thirty-one studies fulfilled the inclusion criteria, with a total of 4662 participants (of which 4522 were receiving the drugs relevant to our comparison) and presented data that could be used for at least one comparison. The trial centres were located in Europe (especially Scandinavia), Japan and Northern America.When comparing perphenazine with placebo, for our primary outcome of clinical response, results favoured perphenazine with significantly more people receiving placebo rated as either 'no better or deterioration' for global state than people receiving perphenazine (1 RCT, n = 61 RR 0.32 CI 0.13 to 0.78, very low quality evidence). More people receiving placebo relapsed, although not a statistically significant number (1 RCT, n = 48, RR 0.14 CI 0.02 to 1.07, very low quality evidence). Death was not reported in the perphenazine versus placebo comparison. Experiences of dystonia were equivocal between groups (1 RCT, n = 48, RR 1.00 CI 0.07 to 15.08, very low quality evidence); other outcomes not reported in this comparison include serious adverse events, economic outcomes, and service use and hospitalisation.For the comparison of perphenazine versus any other antipsychotic drugs, no real differences in effect between the drugs were found. There was no significant difference between groups for those considered 'no better or deterioration' (17 RCTs, n = 1879, RR 1.04 CI 0.91 to 1.17, very low quality evidence). For mental state outcome of 'no effect' of the study drug, there was again no significant difference between groups (4 RCTs, n = 383, RR 1.24 CI 0.61 to 2.52, very low quality evidence). Death was not reported in any of the included studies. There was no significant difference in rates of dystonia with perphenazine versus any other antipsychotic drugs (4 RCTs, n = 416, RR 1.36 CI 0.23 to 8.16, very low quality evidence), nor was there a significant difference between groups for serious adverse events (2 RCTs, n = 1760, RR 0.98 CI 0.68 to 1.41, very low quality evidence). Although perphenazine has been used in randomised trials for more than 50 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. All data for the main outcomes in this review were of very low quality evidence. At best we can say that perphenazine showed similar effects and adverse events as several of the other antipsychotic drugs. Since perphenazine is a relatively inexpensive and frequently used compound, further trials are justified to clarify the properties of this classical antipsychotic drug.

There was high quality evidence to support the effectiveness of topical azelaic acid, topical ivermectin, brimonidine, doxycycline and isotretinoin for rosacea. Moderate quality evidence was available for topical metronidazole and oral tetracycline. There was low quality evidence for low dose minocycline, laser and intense pulsed light therapy and ciclosporin ophthalmic emulsion for ocular rosacea. Time needed to response and response duration should be addressed more completely, with more rigorous reporting of adverse events. Further studies on treatment of ocular rosacea are warranted.

We are grateful to the editors and peer referees who have provided valuable comments on draBs of this update and to Sheila Wallace for her help with the searches. We are also grateful to Dr Karen Boyd for providing information about her trial. We would like to acknowledge the work of all contributors to previous versions of the review, particularly Don Wilson who was responsible for the review from its inception. An earlier version of this review was part of a project to add brief economic commentaries to Cochrane Incontinence's reviews on surgery for urinary incontinence in women (Dean 2017). This project was supported by the National Institute for Health Research (NIHR), via the Cochrane Review Incentive Scheme 2016.

While transvaginal permanent mesh is associated with lower rates of awareness of prolapse, reoperation for prolapse, and prolapse on examination than native tissue repair, it is also associated with higher rates of reoperation for prolapse, stress urinary incontinence, or mesh exposure and higher rates of bladder injury at surgery and de novo stress urinary incontinence. The risk-benefit profile means that transvaginal mesh has limited utility in primary surgery. While it is possible that in women with higher risk of recurrence the benefits may outweigh the risks, there is currently no evidence to support this position.Limited evidence suggests that absorbable mesh may reduce rates of recurrent prolapse on examination compared to native tissue repair, but there was insufficient evidence on absorbable mesh for us to draw any conclusions for other outcomes. There was also insufficient evidence for us to draw any conclusions regarding biological grafts compared to native tissue repair.In 2011, many transvaginal permanent meshes were voluntarily withdrawn from the market, and the newer, lightweight transvaginal permanent meshes still available have not been evaluated within a RCT. In the meantime, these newer transvaginal meshes should be utilised under the discretion of the ethics committee.

Analysis 1.1. Comparison 1 LABA versus placebo: both groups receiving similar dose of ICS, Outcome 1 # participants with exacerbations requiring systemic steroids. . . . . . . . . . . . . . . . . . . . . . . Analysis 1.2. Comparison 1 LABA versus placebo: both groups receiving similar dose of ICS, Outcome 2 # participants with exacerbations requiring hospitalisation. . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.3. Comparison 1 LABA versus placebo: both groups receiving similar dose of ICS, Outcome 3 # participants with exacerbations requiring urgent care visit. . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.4. Comparison 1 LABA versus placebo: both groups receiving similar dose of ICS, Outcome 4 Serious adverse events. . . . . . . . . . . . . . . . . . . . . . . . . . . . .

The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the third update of a review first published in 2007. To assess the efficacy and safety of topical, medical, and surgical treatments for ST of the leg in improving local symptoms and decreasing thromboembolic complications. For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (March 2017), CENTRAL (2017, Issue 2), and trials registries (March 2017). We handsearched the reference lists of relevant papers and conference proceedings. Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the legs that included people with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in a superficial vein. Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus. We assessed the quality of the evidence using the GRADE approach. We identified three additional trials (613 participants), therefore this update considered 33 studies involving 7296 people with ST of the legs. Treatment included fondaparinux; rivaroxaban; low molecular weight heparin (LMWH); unfractionated heparin (UFH); non-steroidal anti-inflammatory drugs (NSAIDs); compression stockings; and topical, intramuscular, or intravenous treatment to surgical interventions such as thrombectomy or ligation. Only a minority of trials compared treatment with placebo rather than an alternative treatment and many studies were small and of poor quality. Pooling of the data was possible for few outcomes, and none were part of a placebo-controlled trial. In one large, placebo-controlled RCT of 3002 participants, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (risk ratio (RR) 0.15, 95% confidence interval (CI) 0.04 to 0.50; moderate-quality evidence), ST extension (RR 0.08, 95% CI 0.03 to 0.22; moderate-quality evidence), and ST recurrence (RR 0.21, 95% CI 0.08 to 0.54; moderate-quality evidence) relative to placebo. Major bleeding was infrequent in both groups with very wide CIs around risk estimate (RR 0.99, 95% CI 0.06 to 15.86; moderate-quality evidence). In one RCT on 472 high-risk participants with ST, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban 10 mg (RR 0.33, 95% CI 0.03 to 3.18; low-quality evidence). There were no major bleeding events in either group (low-quality evidence). In another placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (prophylactic: RR 0.44, 95% CI 0.26 to 0.74; therapeutic: RR 0.46, 95% CI 0.27 to 0.77) and NSAIDs (RR 0.46, 95% CI 0.27 to 0.78) reduced the extension (low-quality evidence) and recurrence of ST (low-quality evidence) in comparison to placebo, with no significant effects on symptomatic VTE (low-quality evidence) or major bleeding (low-quality evidence). Overall, topical treatments improved local symptoms compared with placebo, but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatments, topical treatments, or surgery did not report VTE, ST progression, adverse events, or treatment adverse effects. Prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for ST of the legs for most people. The evidence on topical treatment or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE. Further research is needed to assess the role of rivaroxaban and other direct oral factor-X or thrombin inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment in people at various risk of recurrence; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.